Robert Suchting1, Charles E Green2, Constanza de Dios3, Jessica Vincent3, F Gerard Moeller4, Scott D Lane3, Joy M Schmitz3. 1. Faillace Department of Psychiatry and Behavioral Sciences, UTHealth McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address: Robert.Suchting@uth.tmc.edu. 2. Department of Pediatrics - Center for Clinical Research and Evidence-Based Medicine, UTHealth McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA; MD Anderson - UTHealth Graduate School of Biomedical Sciences, Program in Neuroscience, University of Texas Health Science Center at Houston, Houston, TX, USA. 3. Faillace Department of Psychiatry and Behavioral Sciences, UTHealth McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA. 4. Virginia Commonwealth University, Richmond, VA, USA.
Abstract
BACKGROUND: Medication development research for cocaine use disorder (CUD) has been a longstanding goal in addiction research, but has not resulted in an FDA-approved treatment. Rising cocaine use rates underscore the need for efficient adaptive designs. This study compared differences between two doses of the selective serotonin reuptake inhibitor (SSRI) citalopram (versus placebo) on duration of cocaine abstinence and applied adaptive decision rules to select the 'best efficacy' dose. METHODS: A double-blind, placebo-controlled, randomized Bayesian drop-the-loser (DTL) trial with three arms compared placebo to citalopram 20 mg and 40 mg. Adults (N = 107) with CUD attended thrice-weekly clinic visits for 9 weeks. The primary outcome was longest duration of abstinence (LDA), based on continuous cocaine-negative urine drug screens (UDS). The secondary outcome was probability of cocaine-negative UDS during treatment. A planned interim analysis performed at approximately 50% of recruitment dropped the least-effective active medication. Bayesian inference was used for all analyses with a pre-specified posterior probability (PP) threshold PP ≥ 95% considered statistically reliable evidence RESULTS: Citalopram 40 mg satisfied interim efficacy criteria and was retained for the second half of the trial. For LDA, analyses indicated PP = 82% and PP = 65% of benefit for 40 mg and 20 mg, respectively (each relative to placebo). The odds of having cocaine-negative UDS decreased in all groups over 9 weeks but remained higher for 40 mg (PP = 97.4%) CONCLUSIONS: Neither dose met the 95% PP threshold for the primary outcome; however, 40 mg provided moderate-to-strong evidence for positive effects on LDA and cocaine-negative UDS. The 40 mg dose was declared the "winner" in this DTL trial.
BACKGROUND: Medication development research for cocaine use disorder (CUD) has been a longstanding goal in addiction research, but has not resulted in an FDA-approved treatment. Rising cocaine use rates underscore the need for efficient adaptive designs. This study compared differences between two doses of the selective serotonin reuptake inhibitor (SSRI) citalopram (versus placebo) on duration of cocaine abstinence and applied adaptive decision rules to select the 'best efficacy' dose. METHODS: A double-blind, placebo-controlled, randomized Bayesian drop-the-loser (DTL) trial with three arms compared placebo to citalopram 20 mg and 40 mg. Adults (N = 107) with CUD attended thrice-weekly clinic visits for 9 weeks. The primary outcome was longest duration of abstinence (LDA), based on continuous cocaine-negative urine drug screens (UDS). The secondary outcome was probability of cocaine-negative UDS during treatment. A planned interim analysis performed at approximately 50% of recruitment dropped the least-effective active medication. Bayesian inference was used for all analyses with a pre-specified posterior probability (PP) threshold PP ≥ 95% considered statistically reliable evidence RESULTS: Citalopram 40 mg satisfied interim efficacy criteria and was retained for the second half of the trial. For LDA, analyses indicated PP = 82% and PP = 65% of benefit for 40 mg and 20 mg, respectively (each relative to placebo). The odds of having cocaine-negative UDS decreased in all groups over 9 weeks but remained higher for 40 mg (PP = 97.4%) CONCLUSIONS: Neither dose met the 95% PP threshold for the primary outcome; however, 40 mg provided moderate-to-strong evidence for positive effects on LDA and cocaine-negative UDS. The 40 mg dose was declared the "winner" in this DTL trial.
Authors: Noelle C Anastasio; Sonja J Stutz; Latham H L Fink; Sarah E Swinford-Jackson; Robert M Sears; Ralph J DiLeone; Kenner C Rice; F Gerard Moeller; Kathryn A Cunningham Journal: ACS Chem Neurosci Date: 2015-07-07 Impact factor: 4.418
Authors: Michael J Mancino; Janette McGaugh; Mohit P Chopra; Joseph B Guise; Christopher Cargile; D Keith Williams; Jeff Thostenson; Thomas R Kosten; Nichole Sanders; Alison Oliveto Journal: J Clin Psychopharmacol Date: 2014-04 Impact factor: 3.153
Authors: Maryam Bashiri; Michael J Mancino; Virginia A Stanick; Jeff Thostenson; Thomas R Kosten; Alison H Oliveto Journal: Am J Addict Date: 2017-11-08
Authors: Kyle M Kampman; Kevin G Lynch; Helen M Pettinati; Kelly Spratt; Michael R Wierzbicki; Charles Dackis; Charles P O'Brien Journal: Drug Alcohol Depend Date: 2015-08-14 Impact factor: 4.492
Authors: Dennis J Sholler; Sonja J Stutz; Robert G Fox; Edward L Boone; Qin Wang; Kenner C Rice; F Gerard Moeller; Noelle C Anastasio; Kathryn A Cunningham Journal: J Pharmacol Exp Ther Date: 2018-10-29 Impact factor: 4.030